Activated fibroblasts are the key mediators of fibrosis and these cells are derived from both resident cells as well as from circulating cells termed fibrocytes. Fibrocytes are known to contribute significantly to the total population of fibroblasts in a variety of progressive fibrotic diseases including idiopathic pulmonary fibrosis (IPF), a progressive and fatal form of lung disease for which there are no effective or specific treatments. Others have utilized direct counting of fibrocytes to identify inhibitors of fibrocyte differentiation that reduce the development of fibrosis in animal models, however this method is not amenable to high-throughput drug screening. We have developed a simple and reliable method to quantify fibrocytes that can be used to identify drugs targeting fibrocyte development and differentiation and we demonstrate that this makes small molecule drug discovery efforts against this pathophysiologic target possible. The goal of this Phase I project is to show that our method can be used for high-throughput drug screening (HTS). The ability to undertake HTS will allow us to identify of a new class of specific antifibrotic drugs to treat IPF and related diseases during Phase II. These drugs will serve an unmet clinical need and could reduce the morbidity and mortality associated with fibrotic illnesses and lead to improvements in Public Health. In addition, these compounds may serve as useful biological probes of fibrocyte function. PUBLIC HEALTH RELEVANCE: Fibrocytes are a type of blood cells that are involved in a variety of progressive fibrotic diseases including idiopathic pulmonary fibrosis (IPF), a fatal form of lung disease for which there are no effective or specific treatments. This application aims to demonstrate that the methods that we have developed will allow for high throughput screening (HTS). The ability to undertake HTS will allow for the discovery of drugs targeting fibrocytes. These drugs will serve an unmet clinical need and could reduce the morbidity and mortality associated with fibrotic illnesses and lead to improvements in Public Health.